Rituximab (RTX) is an effective treatment in frequently-relapsing/steroid-dependent nephrotic syndrome (FR/SDNS) in children. However, data regarding the optimal dosing regimen are limited.

Material and methods:

In a multi-center retrospective cohort study at 11 centers in Asia, Europe and North America, children and adolescents with complicated FR/SDNS receiving RTX and followed for at least 18 months from 2005-2016 were included. We examined the effect of RTX prescribed by the three dosing regimens: low (375mg/m2), medium (750mg/m2) and high (1125-1500mg/m2), and concomitant use of immunosuppression (IS).

Results:

Among 517 children (mean age 11.2±4.0, 67.3% boys), 193, 212 and 112 were given low, medium and high dose, respectively. Proportions of children with sustained long-term remission at 12, 18 and 24 months were similar among the regimens. 58.2% children discontinued all IS. 83.1%, 71.3% and 38.8% of patients withdrew concurrent prednisolone, CNI and MMF at a median of 3, 2 and 0.3 months.

Median relapse-free survival of low, medium and high dose were 11.7, 11.9 and 13 months, respectively (p=0.42). When IS was taken into the analyses, relapse-free survival of the regimens was different between the Kaplan-Meier Curves (p=0.005). There was a significant interaction effect between dose and IS. Children receiving high dose of RTX without IS and all regimens with IS were significantly less susceptible to relapse than those given low dose without IS. Adjusted hazard ratios (HRadj) ranged from 0.33 to 0.44 (ps<0.008). Older age at RTX (HRadj=0.95, p=0.005) and Minimal Change Disease on renal biopsy (HRadj=0.7, p=0.02) were favorable predictors of treatment response.

Conclusions:

Rituximab dose and use of concomitant IS have important effects on the long-term control of complicatedFR/SDNS. Children receiving low dose regimen of RTX without IS had the shortest relapse-free survival. Optimal RTX regimen however depends on a balance between efficacy, cost and medication side-effects.